BONE MARROW-DERIVED CELLS FUSE WITH BERGMANN GLIA TO FORM HETEROKARYONS IN A MOUSE MODEL OF MULTIPLE SCLEROSIS

Neurodegenerative diseases represent a growing health challenge with limited therapeutic options. Among emerging strategies, bone marrow-derived cell (BMDC) transplantation shows promise due to the ability of these cells to integrate into the central nervous system through transdifferentiation or cell fusion, forming heterokaryons. BMDC–Purkinje cell fusion has been extensively demonstrated, and the number of fused cells particularly increase under pathological conditions such as experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis.
Using the EAE model, characterized by intense immune infiltration and neuroinflammation, we explored BMDC integration in the cerebellum after GFP+ bone marrow transplantation. Remarkably, we demonstrated for the first time fusion events between BMDCs and Bergmann glia (BG)—specialized astrocytes that support and modulate Purkinje cell function. These fused cells exhibit typical BG morphology and express glial markers such as the Glial Fibrillary Acidic Protein and S100β. Confocal immunofluorescence revealed that these cells were heterokaryons, containing two distinct nuclei distinguished by morphology and by DAPI and active form of RNA polymerase II staining. In addition, we demonstrated that the BMDC nucleus was localized either within the soma or the processes of fused BG.
Our findings provide the first evidence of BMDC–Bergmann glia fusion in EAE mice, uncovering a previously unrecognized mechanism of BMDC integration in the cerebellum and opening new avenues for exploring fusion-based strategies in neuroregeneration.
Support: Funding: MICINN PID2022-140525NB-I00, PID2022-140456NB-I00. Erasmus+ programme Partnership for Cooperation (2023-1-PL01-KA220-HED-000160284). JCyL- FEDER co-funded by the ERDF Operational Programme (CLU-2023-1-01). MIU FPU2020/03457
Contact: pabgonses@usal.es, jorgevalero@usal.es.